This project is a study of the regulatory responses made by the liver to changes in amino acid supply from the diet. The research program initially focuses on parallel changes in protein, RNA an phospholipid content of the liver resulting from changes in the protein content of diet, and progresses to a study of short-term changes in cell metabolism caused by alterations in amino acid supply and eventually proposes to develop an integrated picture of these responses. The current research period will attack this in the following ways: (a) Further studies on the responses of liver protein synthesis and nucleic acid metabolism to changes in amino acid supply. These studies will supplement observations already made in order to provide a more detailed coordination of processes involved in biosynthesis of liver proteins, both secreted and retained, the regulation of RNA metabolism and the possible role of uncharged tRNA as the regulator. (b) Responses of other tissues to changes in amino acid supply. Cells in culture will be used to evaluate similar responses to amino acid supply in order to strengthen our picutre of coordinated control. (c) Identification at the subcellular level of the regulatory mechanism of coordinated responses of liver and other tissues to amino acid supply. This will concentrate on amino acid charging of tRNA, the effect of incomplete charging on ribosome function, and the possible accumulation of regulator molecules from lack of tRNA charging.